PB2107: EVOLUTION OF SELECTION CRITERIA FOR PHASE 3 CLINICAL TRIALS IN MULTIPLE MYELOMA.
Authors: Ernesto Pérez, Idoa Múgica Muñagorri, Adrian Casamayor Garcia, Jorge Illarramendi Esteban, Diana Gisell Gabaldón Limas
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Between 47-72% of patients diagnosed with multiple myeloma (MM) would be excluded from participating in clinical trials due to restrictive selection criteria. This is of particular interest in phase 3 trials, in which some clinical trials are focused on authorization approvals and other to serve as a mirror for real world clinical setting. Since 2017, the ASCO-Friends of Cancer Research published recommendations to modernize the inclusion criteria and favor the inclusion of patients in clinical trials. Aims: We want to analyze the selection criteria of phase 3 clinical trials over the years. Methods: Phase 3 clinical trials registered at clinicaltrial.gov from 2000 to the present have been analyzed, in newly diagnosed and relapsed setting multiple myeloma. Clinical trials for consolidation, maintenance, or conditioning studies for transplantation. We collected data in clinicaltrials.gov and available protocols in the bibliography. ECOG, renal, hepatic and medullary function, neuropathic and infectious disease (HIV, B hepatitis HBV and hepatitis C HCV) and correlated with type of study (diagnosis/relapse), promoter (commercial/non-commercial), type of drug (inhibitors of proteasome-IP-/immunomodulators-IMID) and over 3 periods: P1: 2000-2009; P2: 2010-2015 and P3: 2016-2023. Results: Of the 144 phase-3 clinical trials, 54% had a commercial promoter and 44% were in first line trials. The commercial promoters made mostly in relapse settings (78.2%) while the non-commercial focused on first line (68%), p=0.000. No differences were observed on selection criteria between commercial and non-commercial except for liver function, where non-commercial promoters were more restrictive: upper limit of normality (ULN) for AST and ALT up to 3 times: 71% vs. 31%, p: 0.017. At relapse setting, clinical trials were more permissive than those at diagnosis in liver function (ASL up to >=3 ULN 60% vs 38%, p:0.044, respectively) and the presence of neuropathy (up to grade 2 neuropathy allowed in 78.6% vs 19.4%, p:0.000, respectively). Regarding periods, during P1 16% allowed inclusion patients with an ECOG up to 3, compared 3% and 2%, respectively in P2 and P3 (p:0.017). Patients with HIV, HBV and HCV but with negative PCR were increasingly allowed in clinical trials throughout the periods: HIV: 25%; 31%; 43% (p: 0.369); HBV; 64%; 60%; 84% (p: 0.079), and HCV: 57%; 52%; 87% (p: 0.007), in P1, P2 and P3 respectively. No differences have been observed on grade of neuropathy or hematological counts throughout the three periods. Finally, regarding drugs, studies that include PI were more restrictive in terms of bilirubin ULN: up to 2 ULN: 60% vs 37%; p: 0.033) and at least 75,000/mm3 platelets: 56% for studies with PI vs 34% without PI; p: 0.039; while clinical trials with IMID, paradoxically, were more restrictive for neuropathy: up to grade 2: 43% vs 73%; p: 0.16 and low limit of platelets count: <75,000/mm3: 39% vs 81%, p: 0.02. Summary/Conclusion: We observed small differences between the clinical trials promoted by the industry and academic entities. Relapsed trials tend to be permissive in terms of neuropathy and liver involvement, reflecting the complexity of these patients. There is greater permissively for HIV, HBV and HCV infections but with negative PCR, possibly due to the availability of new treatments and the more favorable prognosis of these pathologies than in previous years. However, in the last period we have observed higher restriction in the ECOG setting. It is necessary to improve the selection criteria to generalize the inclusion of patients.Keywords: Multiple myeloma, Clinical trial, Relapse